Study design for measurement of apixaban pharmacokinetics and pharmacodynamics in five horses. Apixaban (0.15–0.2 mg/kg) or placebo were administered orally (per os, PO) or intravenously (IV) just after baseline (0) blood samples were taken (upward blue arrow). The PO or IV routes were randomized for each horse in the following order: IV, PO, PO, IV, with each administration being followed by a 14-day washout. Blood samples were collected into 3.8% citrate anticoagulant at 0, 3 (IV only), 15 (PO only), 30, and 45 minutes (min), and 1, 2, 3, 4, 6, 8, and 24 hours (h) after drug or placebo administration for ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and anti-activated factor X (Anti-Xa) activity and dilute prothrombin time (dPT) assays on platelet-poor plasma. Flow cytometry (Flow) for quantification of P-selectin expression in agonist-activated platelets was performed at 0, 2, and 24 h in citrate-anticoagulated platelet-rich plasma. Blood was collected into EDTA- and non-anticoagulant vacutainer tubes at 0 and 24 h for a complete blood count (CBC) and select biochemical (Chem) tests, respectively.

Mean apixaban plasma concentration (line) and individual data (•) after a bolus intravenous administration of 0.15 mg/kg to five horses before drug administration (time 0) and at 3, 30, 45 min, and 1, 2, 3, 4, 6, 8, and 24 h after drug administration measured by ultra performance liquid performance-mass spectrometry. The data represents a two-compartment pharmacokinetic curve, with a rapid initial phase of decline, followed by a slower and longer phase of elimination. Mean concentrations in samples collected after 6 h were below the detection limit of the assay.